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Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>), rhBMP-2 (1.5\u00a0\u00b5g), or a combination of sEVs and rhBMP-2 (<jats:italic>n<\/jats:italic>\u2009=\u200916 for each group). 6 weeks post-surgery, femora were evaluated by \u00b5CT, descriptive histology, and biomechanical testing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Native radiographs and \u00b5CT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13287-024-03755-8","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T01:01:18Z","timestamp":1716166878000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-7371","authenticated-orcid":false,"given":"Amelie","family":"Deluca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Heimel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Deininger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Wichlas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Redl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Rohde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Tempfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Gimona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Traweger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"issue":"1","key":"3755_CR1","doi-asserted-by":"publisher","first-page":"46","DOI":"10.5152\/eurjrheum.2016.048","volume":"4","author":"T S\u00f6zen","year":"2017","unstructured":"S\u00f6zen T, \u00d6z\u0131\u015f\u0131k L, Ba\u015faran N. 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(1) Title of the approved project: \u201cRegeneration of a metaphyseal defect in osteoporotic rats by implantation of exosomal vesicles\u201d; (2) Name of the institutional approval committee: Federal Ministry of Education, Science and Research \u2013 V\/3b (Animal testing and genetic engineering); (3) Approval Number: 2020\u2009\u2212\u20090.547.757; (4) Date of approval: 24. 09. 2020 The collection of human umbilical cord for isolation of mesenchyma stromal cells and enrichment of extracellular vesicles has been approved by the Ethics Commission for the State of Salzburg and informed consent was obtained from all donors (1). Title of the approved project: \u201cCharacterization of somatic cells and stem cells from human umbilical cord tissue\u201d; (2) Name of the institutional approval committee: Ethics Commission for the State of Salzburg; (3) Approval Number: 415-E\/1547\/2-2012; (4) Date of approval: 05.11.2012.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"144"}}